The specific aims of the project are to determine the sequence and nature of microvascular events in skeletal muscle, intestinal and cerebral cortical vasculature during diabetes mellitus. In addition, a correlation of the severity of microvascular disturbances and hyperglycemia will be made. These specific aims will be accompanied by the development of chronic and semi-chronic preparations of the small intestine for study of normal and pathological vascular behavior. The sequence of vascular changes after adult onset diabetes will be studied by measurement at two weeik intervals of microvascular dimensions and pressures, tissue PO2, number and distribution of microvessels and reactivity of microvessels to dilating agents. To correlate hyperglycemia to vascular disturbances, diet restriction of Db/Db mice will be used to produce gradations of hyperglycemia: vascular measurements will be the same as above. The overall results will be used to determine which diabetic vascular problems develop first and whether their development is a function of the severity of hyperglycemia.